The proposed project will provide a detail of the patterns of staining with antisera to Tau in human autopsy brain. It will provide the morphological correlates for the quantitative assessments that Dr. Binder will be performing in Project 4. This project involves a series of experiments designed to: 1) identify the ideal fixative in postmortem state for antisera directed against Tau and multiple other cytoskeletal elements, 2) identify those brain regions that have a consistent staining pattern with antisera to Tau and that also manifest age related alterations such as dystrophic neurites and abnormal perikaryal staining. Fifteen cases from clinically characterized non-demented individuals whose ages match those of 15 cases with Alzheimer's Disease will be identified. In these two groups the patterns and distributions of abnormally stained structures will be compared after staining with Tau antisera. Structural abnormalities will be quantitated through the use of computer assisted morphometry systems. In addition, a variety of other antisera will be employed to assess alteration in the microtubule and neurofilament systems. Dr. Binder will be provided with fresh frozen blocks adjacent to those regions that are morphologically characterized. Thus, Dr. Binder will be able to correlate Tau content to structural abnormalities, as well as plaque, tangle and dystrophic neurite counts performed with silver stains.